Mercaptoethyl carbamates



United States Patent 12 Claims. (Cl. 260-482) This application is a division of the US. patent application of Delbert D. Reynolds, Serial No. 105,568, filed April 26, 1961, now Patent No. 3,213,091, for Mercaptoethylation of Amines With Ethylene Monothiolca-r-bonate and Z-Mercaptoethylcarbonates which was a continuationin part of and copending with application Serial No. 721,678, filed March 17, 1958, now abandoned, said application Serial No. 721,678 having been a continuation-in-part of and copendin-g with application Serial No. 647,499, filed March 21, 1957, now US. Patent 2,828,318.

This invention concerns a process for introducing the mercaptoethyl radical into amines, more particularly mercaptoethylating amines, and preparing 2-mercaptoethyl carbamates.

Mercaptans and their derivatives are required for use in many applications, particularly for use in the rubber industry, as disclosed by H. R. Snyder et al., J. Amer. Chem. Soc., 69, 2672 (1947). They are also useful in the pharmaceutical field as disclosed by R. 0. Clinton et. al., J. Amer. Chem. Soc., 70, 950 (1948), and in the photographic industry in photographic emulsions and the like.

One broad class of useful mercaptan derivatives is the mercaptolethyl derivatives, in particular those derived from amines and having the general formula where R and R are hydrogen, alkyl, aryl or aralkyl. Three methods have customarily been used to synthesize these compounds. One involves the reaction of aminoethy-l halides with hydrosulfides of the alkali metals. Another is based on the condensation of aminoethyl halides with thiourea followed by alkaline hydrolysis. A third and more preferred method is the mercaptoethylation of primary and secondary amines by reaction with ethylene sulfide. This process leaves much to be desired because of the difiiculties encountered in handling ethylene sulfide. Ethylene sulfide readily polymerizes and cannot be stored safely in large quantities. Hence this process is not suitable for mercaptoethylation on a large scale.

In my US. Patent' No. 2,828,318, which was issued March 25, 1958, a process is disclosed for preparing ethylene sulfide which involves the thermal decomposition of ethylene monothiolcarbonate according to the following equation:

The ethylene monothiolca-rbonate is a high-boiling liquid which is stable under normal conditions and therefore, unlike ethylene sulfide, it can be kept for extended periods of time. Like ethylene sulfide, however, it reacts with primary or secondary amines to yield mercapto derivatives. v

One object of this invention is to obtain mercaptoethyl derivatives by the mercaptoethylation of primary or "ice secondary amines. Another object is to provide a mercaptoethylation process which avoids the difficulties inherent in using ethylene sulfide due to its inclination for polymerization. An additional object is to obtain mercaptoethy'l derivatives.

The invention is illustrated by the reaction in which ethylene monothiolcarbonate is treated with greater than one mole of a typical amine to yield an aminoethanethiol and carbon dioxide. This reaction can be called mercaptoethylation of an amine.

Ethylene m-onothiolcarbonate may be reacted with one mole or less of any primary or secondary amine which may be aliphatic or cyclic to form carbamates. Any amine with a replaceable hydrogen atoms is operative in this process including dia-mi-nes. The resulting product has a general formula of G[CO CH CH SH] or of G[CO CH CH S(Q)] in which n is 1 or 2, and G and Q are defined herein. The preparation of these carbamates is-preferably carried out at 0 to 25 C.

Primary and secondary mercaptoethylamines which are aliphatic, aromatic, or cyclic may be prepared by reacting the amines with B[CO CH CH S(Q)] (i.e., merca-ptoet-hylating amines using Z-mercaptoethyl carbamates) where B is G, anilino, alkyl or alkoxy (C -C ring-substituted aniline, halogen-substituted anilino, and phenylenediamino. When B is derived from an aromatic amine, the B[CO CH CH S(Q)] is obtainable from reacting the coresponding isocyanate or diisocyante with and a basic catalyst is required in its subsequent use as a mercaptoethylating agent.

The process may be carried out by merca ptoethylating primary and secondary amines which are aliphatic, aromatic, or cyclic amines 'by reacting ethylene .monothiolcarbonate with greater than one mole of amines.

When pure, ethylene monothiolcarbonate is stable at reflux temperature (237'C.). However, in the presence of a base, including amines, it decomposes to yield ethylene sulfide and CO However, an alkaline catalyst such as sodium methoxideis required to decompose the ethylene monothiolcarbonate when the amine reactant is aromatic. The ethylene sulfide then reacts with the amine to form a merca-ptoethylamine.

In general, any amino function in the presence of other nonparticipating function, for example, polyamines, polyimines, amino acids, polypeptides, proteins, amino sugars, deacetylated chitin, gelatin, and the like can be mercaptoetbyl-ated.

Using the process of reacting ethylene monothiolca-rbonate with one mole or less of an amine, new car-bamates can be prepared which are mercaptoethylating agents of the formula: 1

G 2 2 2 (Q) in in which the Q may be H, COR, CO R, COG and 0(NH)NH -HX in which X may 'be chloride or bromide; and n may be 1 or 2. When n is 1, G may be RHN, RR N, and ZN, where R is alkyl (C -C or cycloalkyl and Z may be 4 or 5 atoms necessary to complete a heterocyclic ring with N. The atoms may be all carbon atoms or an oxygen or nitrogen atom combined with three or more carbon atoms. When n is 2, G may be Y Y Y where Y ishydrogen or R (defined above) and .x is 2 to 18.

The folowing examples are intended to ilustrate my invention but are not intended to limit it in any way.

Example 1. Ethylene monothiolcarbonate drate and 1.5 l. of benzene was refluxed for 4 hours under an 18" glass-helices packed distillation apparatus. During this period the benzene-water-a'lcohol and then the benzene-alcohol azeotropes were continuously distilled at a rate to maintain a stillhead temperature of 70 C.

The reaction mixture wascooled and the polymer formed during the reaction further precipitated by the addition, with stirring, of 1.5 l. of ether. After filtering off the polymer, the acidic filtrate was neutralized with an aqueous sodium carbonate solution (62.0 g., 0.05 mole, of sodium carbonate in 500 ml. of water) and the pH adjusted to about 6 by the addition of ml. of glacial acetic acid. The organic layer was separated, stabilized with 20.0 g. of stearic acid, and distilled under reduced pressure through an 18" glass-helices packed column to yield 384 g. (73.6 percent) of product, B.P. 75/1.0 mm., r1 1.5104. To prevent possible contamination of product during distillation, it was found necessary to remove a small amount of white crystalline material identified as 1,4-dithiane (M.P. 105. Calcd.: C, 40.0; H, 6.7. Found: C, 39.5; H, 6.5.)'-from the cold finger just prior to the distillation of the ethylene monothiolcarbonate.

Example 2.-2-diethylaminoerhanethial One mole (73 g.) of diethylamine was refluxed with 150 ml. of anhydrous toluene. One-half mole (52 g.) of ethylene monothiolcarbonate was added through a dropping funnel and the refluxing continued for sixteen hours. The toluene was removed under reduced pressure, and the reaction products distilled at 83-85" at 57 mm. through a 10" x 1 glass column packed with glass helices, and equipped with a variable-take-oif still head. Fortyone and five-tenths g. (62.4 percent) of 2-diethylaminoethanethiol were collected, n =1.4650. Redistillation' of 84-85 at 55 mm. gave n =1.4632.

Analysis.Calcd for C H NS: C, 54.1; H, 11.3; N, 10.5; S, 24.1. Found: C, 54.1; H, 11.3; N,-10.3; S, 23.9.

A higher boiling fraction (7.5 g.) B.P. 85-150 at 57 mm. was obtained from this first distillation. A high sulfur and low carbon also low nitrogen content indicates it is composed of high mercaptoethylation products.

Example 3.2-di-n-butylaminoethanethiol Example 4.2-piperidin0ethanethiol One mole of piperidine (85 g.) was refluxed in 150 ml. of anhydrous toluene. One-half mole of ethylene monothiolcarbonate was added and the refluxing continued for seventeen hours. The toluene and excess piperidine were distilled at atmospheric pressure through a 12" glass packed column. The undis-tilled productcontained some piperidine carbonate. After cooling, it was mixed with 400 ml. of ether and washed with 100 ml. 'of cold water. After drying over MgSO the ether was distilled. The Z-piperidinoethanethiol (51 g.) distilled at 84 at 14 mm. n =l.4989. Yield 70%.

4 Analysis.Calcd for C H 5NS: C, 58.0; H, 10.3; N, 9.7; S, 22.0. FoundzC, 57.9; H, 10.5; N, 9.7; S, 21.5.

Example 5 .--2-morpholinoethanethiol One mole of morpholine (87 g.) was refluxed in 15.0 ml. anhydrous toluene. After adding 52 g. (0.5 mole) of ethylenemonothiolcarbonate the solution was refluxed for seven hours. After, cooling, the solution was washed with cold water to remove morpholine carbonate. Distillation yielded 42 g. of 2-mor-pholinoethanethiol (57%) n =l.5O22.

Analysis.CalCd for C H NOS: C, 48.9; H, 8.8; N, 9.5; S, 21.8. Found: C, 48.8; H, 8.7;N, 9.0; S, 21.7.

Example 6.2-benzylamin0ethanethi0l One mole of benzylamine (107 g.) was refluxed in 150 ml. of anhydrous toluene. One-half mole of ethylene monothiolcarbonate was added and refluxing continued for eighteen and one-half hours. The reaction mixture was washed with 200 ml. of cold water, dried over -MgSO and distilled. Fifty-three g. (63%) of 2-benzylarninoethancthiol was obtained; B.P. 97-110 at 0.8-1.2 mm. n =1.559O.

Analysis.Calcd, for C H NS: N, 8.4; S, 19.1. Found: N, 8.6; S, 19.3.

Example 7.-Di-n-butylaminaethylmercaptoethanethiol A mixture of 60 g. of di-nbutylaminoethanethiol (0.32 mole), from Example 3, 100 ml. of anhydrous toluene, and 34 g. of ethylene monothiolcarbonatewas refluxed for seventeen hours. The reaction mixture .was washed with 200 ml. of water and dried over, MgSO After removal of the toluene, the product was fractionated.

Fraction 3 represents a 45% yield.

Analysis.Calcd for C H NS C, 57.8; H, 10.8;-N, 5.6; S, 25.7. Found: C, 57.9; H, 10.6; N, 5.6;S, 25.6.

Example 8 Since, many amines have low-boiling points, very low reaction temperatures are obtained at normal pressure. With aromatic amines a basic catalyst, such as sodium methoxide, is used. By conducting the reaction in a rocking-type autoclave, employing a positive displacement pump to meter the ethylene monothiolcar-bonate into. the amine-solvent mixture, yields can be significantly improved. A 7 percent yield of 2-isopropylaminoethanethiol was obtained by employing a reaction temperature of about 50 C. at atmospheric pressure.

A 77 percent yield was. obtained of 2-isopropyl-aminoethanethiol by conducting the reaction at C. for 15 minutes in an autoclave. Similar increases in yields. were obtained for a number of other low-molecularweight amines, which are marked with an asterisk in Tables I and II, following Example 9. In each instance, the pressure was that generated by the reaction.

Example 9 Ethylene monothiolcarbonate was refluxed with a series of arnmes using a twofold molar. excess of the amines, refluxing the amines with the ethylene monothiolcarbonate in toluene overnight using an eflicient condenser.

TABLE III 2-MERCAPTOETHYL CARBAMATES G[COH1CH SH].,

Percent Yield for Re- Analysis, percent action Time (hrs) of G n B.P./mm. m. Calculated Found 60 90 170 0r M.P.( C.)

o H N s o H N s 7 n-C4H NH- 1 80 98/0. 5 1. 4782 47. 5 8. 5 7. 9 18. 1 47. 4 8. 6 7. 9 18.1 n- C5H13NH 1 83 134/0. 3 1. 4755 52. 7 9. 3 6. 8 15. 6 52. 7 8. 9 7. 2 15. 7 CHz=CH CHzNH- 1 43 69 81 83/0. 2 1. 4978 44. 7 6. 8 8. 7 19.9 43. 9 6. 9 8. 4 20. 1 (CH3)2CHNH' 1 10 44 60 93/1. 0 1. 4792 44. 2 8. 0 8. 6 19. 6 44. 6 8. 4 8. 8 19. 6 (l1C4Hg)gN- 1 0 34 106/0. 6 1. 4660 56. 7 9. 9 6. 0 l3. 7 57. 2 10. 2 6. 2 l4. 0

8 CHaN N- 1 82 118/1. 0 1. 5078 47. 1 7. 8 13. 7 15. 7 46. 8 8. 1 13. 6 15. 5

9 C911 CHgNH- 1 56 151/1. 05 1. 5531 56.8 6. 2 6. 6 15. 2 67. 6 6. 6 7. 6 i 15. 2

11 HN CHiCHzNH- 2 101-104 35. 8 6.0 10. 4 23. 9 36. 6 6. 5 9. 9 23. 9

Example 11 sion layers subsequent to development in order to sta- TABLE IV bilize the silver image. Instead of procedure the aminoethanethiols may be applied to the developed print in vapor form from a boiling aqueous solutionwith the result that a stable silver complex is formed. This procedure obviates the usual fixing and washing steps. However, the aminoethanethiols may be used in solutions for fixing prints in the usual manner, in which case they form soluble salts with the residual silver halide which can Percent Yield Percent Purity 01' Q 6 NCHaCHgSH 0 N CH: CHzSH O N-' H 87 C H5NH- H 85 l1- C4H9NH H 74 n- C|HONH C O CsH -n 68 98 Il-C4H NH COzCuHrs-H 72 97 n- C4H NH- C (=NH) NHz-H Cl 47 98 n-C4H NH-- CONH C4H9-n 65 99 My process of mercaptoethylating amines with ethylene monothiolcanbonate has many advantages over systems using ethylene sulfide since my mercaptoe-thylating agent is stable and may be stored under normal conditions. Good yields of mercaptoethylated products are obtained without formation of polyethylene sulfide. This new process of mercaptoethyl'ating amines is to be preferred over the reactions involving Z-chloroethylamines because of the more readily available starting materials.

The reactants can be dissolved in suitable inert common solvents, such as toluene, dioxane, xylene and the 70 like and heated to the reflux temperature of the solvent used.

The aminoethanethiols of this invention may be used in photography for .various purposes. For example, it is well known in photography to fixv silver halide emulbe readily washed out of the print. 'Ilhe solutions may further contain organic colloid hardening agents such as aluminum formoacetate, 'glutaraldehyde and potassium alum. The aminoth iols will dissolve silver halide in acid solution whereas thiols lacking an amino substituent, such as mercaptoacetic acid, require alkaline conditions for fixing.

The invention has been described in detail with particul-ar reference to the preferred embodiments thereof, but itwill be understood that variations and modifications can be elfeeted within the spinit and scope of the invention, as described hereinabove, and as defined in the appended claims.

I claim:

1. A compound selected from the group consisting of 1,4-piperazine bis mercaptoethyl carhamate, 1,2-ethylene- 9 diamine bis mercaptoethyl carbamate and those having the formula GCO CH CH SH wherein G is selected from the group consisting of N, 6 N, H3CN N- CH =CHCH NH, C H CH NH-, and RRN- wherein R is selected from the group consisting of hydrogen and R, and wherein R is an alkyl radical having from 1-18 carbon atoms.

2. A compound having the formula 11-C H NHCO CH CH SH 3. A compound having the formula Il-CsHnNHCOzCHgCHzSH 4. A compound having the formula CH =CHCH NHCO CH CH SH 5. A compound having the formula (CH CHNHCO CH CH SH 6. A compound having the formula (H'C4Hg) NCO CH CH SH 7. The process which comprises contacting ethylene monothiolcarbonate with up to a stoichziometric equivalent of an organic monoamine selected from the group consisting of pyridine, morpholine, N-methylpiperazine, allylamine, benzylamine and R,R'N wherein R is selected from the group consisting of hydrogen and R, and wherein R is an alkyl radical having from 1 to 18 carbon atoms and recovering a Z-mercaptoethyl carbamate.

8. The process which comprises contacting ethylene monothiolcarbanate with up to a stoichiometric equiva lent of an organic monoamine of the formula n-C H NH and recovering 2-mercapto-ethy1 carbamate.

9. The process which comprises contacting ethylene monothiolcarbonate with up to a stoichiometric equivalent of an organic monoamine of the formula n-C H -NH and recovering Z-mercapto-ethyl car-bamate.

10. The process which comprises contacting ethylene monothiolcar'bonate with up to a stoichiometric equivalent of an organic monoamin'e of the formula CH =CHCH NH and recovering Z-mercaptoethyl carbarnate.

11. The process which comprises contacting ethylene monothiolcarbonate with up to a stoiohiometric equivalent of an organic monoamine of the formula (CH CHNH and recovering Z-mercapto-ethyl carbarnate.

12. The process which comprises contacting ethylene monothiolcarbonate with up to a stoichiometric equivalent of an organic monoamine of the formula and recovering 2-rmencapto-ethy1 carbamate.

References Cited by the Examiner UNITED STATES PATENTS 2,802,022 8/1957 Groszos et a1. 260482 2,806,838 9/1957 Melamed 260471 3,072,676 1/ 1963 Johnson et al 260-482 3,076,007 1/ 1963 Barclay et al. 2 --453 FOREIGN PATENTS 476,305 12/ 1952 Italy.

OTHER REFERENCES Conant, The Chemistry of Organic Compounds (textbook), pages 264-269 (1939).

LORRAINE A. WEINBERGER, Primary Examiher.

A. P. HALLUIN, Assistant Examiner. 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF 1,4-PIPERAZINE BIS MERCAPTOETHYL CARBAMINE, 1,2-ETHYLENEDIAMINE BIS MERCAPTOETHYL CARBAMATE AND THOSE HAVING THE FORMULA GCO2CH2CH2SH WHEREIN G IS SELECTED FROM THE GROUP CONSISTING OF PIPERIDINO, MORPHOLINO, 4-(CH3-)PIPERAZINO, CH2=CHCH2NH-, C6H5CH2NH-, AND RR''NWHEREIN R IS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN AND R'', AND WHEREIN R'' IS AN ALKYL RADICAL HAVING FROM 1-18 CARBON ATOMS.
 7. THE PROCESS WHICH COMPRISES CONTACTING ETHYLENE MONOTHIOLCARBONATE WITH UP TO A STOICHIOMETRIC EQUIVALENT OF AN ORGANIC MONOAMINE SELECTED FROM THE GROUP CONSISTING OF PYRIDE, MORPHOLINE, N-METHYLPIPERAZINE, ALLYLAMINE, BENZYLAMINE AND R,R''N WHEREIN R IS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN AND R'', AND WHEREIN R'' IS AN ALKYL RADICAL HAVING FROM 1 TO 18 CARBON ATOMS AND RECOVERING A 2-MERCAPTOETHYL CARBAMATE. 